U.S. patent application number 17/254437 was filed with the patent office on 2021-07-22 for method for producing fluorinated compound.
This patent application is currently assigned to DAIKIN INDUSTRIES, LTD.. The applicant listed for this patent is DAIKIN INDUSTRIES, LTD., UNIVERSITY PUBLIC CORPORATION OSAKA. Invention is credited to Takahide FUKUYAMA, Yosuke KISHIKAWA, Yoshichika KUROKI, Makoto MATSUURA, Ilhyong RYU.
Application Number | 20210221766 17/254437 |
Document ID | / |
Family ID | 1000005549815 |
Filed Date | 2021-07-22 |
United States Patent
Application |
20210221766 |
Kind Code |
A1 |
MATSUURA; Makoto ; et
al. |
July 22, 2021 |
METHOD FOR PRODUCING FLUORINATED COMPOUND
Abstract
An object of the present invention is to provide a novel method
for producing a fluorine-containing methylene compound. The above
object can be achieved by a method for producing a compound
represented by formula (1): ##STR00001## wherein R.sup.1 represents
an organic group, R.sup.A represents hydrogen or fluorine, R.sup.4a
represents hydrogen or an organic group, R.sup.4b represents
hydrogen or an organic group, R.sup.5a represents hydrogen or an
organic group, R.sup.5b represents hydrogen or an organic group,
and R.sup.2 represents hydrogen or an organic group; R.sup.2 is
optionally connected to R.sup.4a to form a ring; the method
comprising step A of reacting a compound represented by formula
(2): ##STR00002## wherein X.sup.1 represents a leaving group, and
other symbols are as defined above, with a compound represented by
formula (3): ##STR00003## wherein X.sup.2 represents a leaving
group, and other symbols are as defined above, in the presence of a
reducing agent as desired, under light irradiation.
Inventors: |
MATSUURA; Makoto; (Osaka,
JP) ; KUROKI; Yoshichika; (Osaka, JP) ;
KISHIKAWA; Yosuke; (Osaka, JP) ; RYU; Ilhyong;
(Osaka, JP) ; FUKUYAMA; Takahide; (Osaka,
JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
DAIKIN INDUSTRIES, LTD.
UNIVERSITY PUBLIC CORPORATION OSAKA |
Osaka
Osaka |
|
JP
JP |
|
|
Assignee: |
DAIKIN INDUSTRIES, LTD.
Osaka
JP
UNIVERSITY PUBLIC CORPORATION OSAKA
Osaka
JP
|
Family ID: |
1000005549815 |
Appl. No.: |
17/254437 |
Filed: |
June 20, 2019 |
PCT Filed: |
June 20, 2019 |
PCT NO: |
PCT/JP2019/024610 |
371 Date: |
December 21, 2020 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07C 67/347 20130101;
B01J 2531/821 20130101; B01J 2231/4294 20130101; B01J 31/1815
20130101; C07C 67/343 20130101; C07C 37/62 20130101 |
International
Class: |
C07C 67/347 20060101
C07C067/347; C07C 67/343 20060101 C07C067/343; C07C 37/62 20060101
C07C037/62; B01J 31/18 20060101 B01J031/18 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 22, 2018 |
JP |
2018-119223 |
Claims
1. A method for producing a compound represented by formula (1):
##STR00057## wherein R.sup.1 represents an organic group, R.sup.A
represents hydrogen or fluorine, .sub.R.sup.4a represents hydrogen
or an organic group, R.sup.4b represents hydrogen or an organic
group, R.sup.2 represents hydrogen or an organic group, R.sup.4a
represents hydrogen or an organic group, and R.sup.5b resents
hydrogen or an organic group; or R.sup.2 is optionally connected to
R.sup.4a to form a ring; the method comprising step A of reacting a
compound represented by formula (2): ##STR00058## wherein X.sup.1
represents a leaving group, and other symbols are as defined above,
with a compound represented by formula (3): ##STR00059## wherein
X.sup.2 represents a leaving group, and other symbols are as
defined above, in the presence of a reducing agent as desired,
under light irradiation.
2. The production method according to claim 1, wherein R.sup.1
represents R.sup.11--Y-- or (R.sup.11--).sub.2N--, Y represents a
bond, oxygen, or sulfur, and R.sup.11 independently represents, in
each occurrence, a hydrocarbon group that optionally has one or
more sub stituents.
3. The production method according to claim 2, wherein R.sup.1
represents R.sup.11--Y--, Y represents a bond, and R.sup.11
represents an aryl group that optionally has one or more
substituents, or an alkyl group that optionally has one or more sub
stituents.
4. The production method according to claim 2, wherein R.sup.1
represents R.sup.11--Y--, Y represents --O--C(.dbd.O)-- or
--O--C(.dbd.S)--, and R.sup.11 represents an aliphatic hydrocarbon
group that optionally has one or more substituents.
5. The production method according to claim 2, wherein R.sup.1
represents (R.sup.11--).sub.2N--C(.dbd.O)-- and R.sup.11
independently represents, in each occurrence, an aliphatic
hydrocarbon group that optionally has one or more substituents.
6. The production method according to claim 1, wherein R.sup.A
represents fluorine.
7. The production method according to claim 1, wherein R.sup.4a
represents hydrogen, R.sup.4b represents hydrogen, R.sup.2
represents hydrogen, a hydrocarbon group that optionally has one or
more substituents, or an alkoxycarbonyl group that optionally has
one or more substituents, R.sup.5a represents hydrogen, and
R.sup.5b represents hydrogen.
8. The production method according to claim 1, wherein X.sup.1
represents halogen, an alkylsulfonyloxy group, or an
arylsulfonyloxy group.
9. The production method according to claim 1, wherein X.sup.2
represents --SO.sub.2R, --SR, --S(.dbd.O)R, --SeR, --TeR, --Cl
--Br, --I, --PR.sub.2, or --P(.dbd.O)R.sub.2, wherein R
independently represents, in each occurrence, an organic group.
10. The production method according to claim 9, wherein X.sup.2
represents --SO.sub.2R, wherein R is an organic group.
11. The production method according to claim 1, wherein the
reducing agent is a nitrogen-containing unsaturated heterocyclic
compound having an N--H moiety.
12. The production method according to claim 1, wherein the
reducing agent is a compound represented by formula (4):
##STR00060## wherein R.sup.ha, R.sup.hb, R.sup.hc and R.sup.hd are
the same or different, and each represents alkyl.
13. The production method according to claim 1, wherein the
reaction of step A is performed in the presence of a catalyst.
14. The production method according to claim 13, wherein the
catalyst is at least one member selected from the group consisting
of transition metal complexes and organic dye compounds.
15. A method for producing a compound represented by formula (la):
##STR00061## wherein R.sup.1 independently represents, in each
occurrence, an organic group, R.sup.A independently represents, in
each occurrence, hydrogen or fluorine, R.sup.4a independently
represents, in each occurrence, hydrogen or an organic group,
R.sup.4b independently represents, in each occurrence, hydrogen or
an organic group, and R.sup.2 represents hydrogen or an organic
group; the method comprising step Aa of reacting a compound
represented by formula (2): ##STR00062## wherein X.sup.1 represents
a leaving group, and other symbols are as defined above, with a
compound represented by formula (3): ##STR00063## wherein X.sup.2
represents a leaving group, and other symbols are as defined above,
in the presence of a reducing agent as desired, under light
irradiation.
16-25. (canceled)
Description
TECHNICAL FIELD
[0001] The present invention relates to a method for producing a
fluorine-containing compound.
BACKGROUND ART
[0002] Since some physiologically active substances in vivo are
fluorinated methylene-containing compounds, applications of
fluoromethylene-containing compounds to, e.g., drugs have been
actively studied.
[0003] For example, methods for producing fluorine-containing
methylene compounds, such as .alpha.-fluoromethylene compounds and
.alpha.-difluoroaldol compounds, which are carbonyl compounds
having, at the .alpha.-position, at least one substituent selected
from the group consisting of fluorine atoms and perfluoro organic
groups, are highly useful (Non-patent Literature 1 and 2).
[0004] As one example of the method for producing a
fluorine-containing methylene compound, Patent Literature 1
discloses the following.
[0005] A method for producing a compound represented by formula (1)
or a ring-closed or ring-open derivative of the compound:
##STR00004##
wherein R.sup.1 represents an organic group, R.sup.X represents
hydrogen or fluorine, R.sup.2a, R.sup.2b, R.sup.2c, and R.sup.2 are
the same or different, and each represents --Y--R.sup.21 or
--N(--R.sup.22).sub.2, or R.sup.2b may be connected to R.sup.2c to
form a bond, wherein Y represents a bond, oxygen, or sulfur,
R.sup.21 represents hydrogen or an organic group, and R.sup.22, in
each occurrence, is the same or different, and represents hydrogen
or an organic group; the method comprising step A of reacting a
compound represented by the following formula (2):
##STR00005##
wherein X represents a leaving group, and other symbols are as
defined above, with a compound represented by the following formula
(3):
##STR00006##
wherein the symbols are as defined above, in the presence of a
reducing agent under light irradiation.
CITATION LIST
Patent Literature
[0006] PTL 1: Pamphlet of WO2017/154948
Non-Patent Literature
[0007] NPL 1: John T. Welch et al., Tetrahedron, 1987, 43, 14,
p.3123
[0008] NPL 2: Svante et al., J. Am. Chem. Soc., 1981, 103,
p.4452
SUMMARY OF INVENTION
Technical Problem
[0009] However, another novel method for producing a
fluorine-containing methylene compound is desired.
[0010] The present disclosure aims to provide a novel method for
producing a fluorine-containing methylene compound.
Solution to Problem
[0011] The present disclosure includes the following
embodiments.
[0012] Item 1. A method for producing a compound represented by
formula (1)
##STR00007##
wherein R.sup.1 represents an organic group, R.sup.A represents
hydrogen or fluorine, R.sup.4a represents hydrogen or an organic
group, R.sup.4b represents hydrogen or an organic group, R.sup.2
represents hydrogen or an organic group, R.sup.5a represents
hydrogen or an organic group, and R.sup.5b represents hydrogen or
an organic group; or R.sup.2 is optionally connected to R.sup.4a to
form a ring; the method comprising step A of reacting a compound
represented by formula (2):
##STR00008##
wherein X.sup.1 represents a leaving group, and other symbols are
as defined above, with a compound represented by formula (3):
##STR00009##
wherein X.sup.2 represents a leaving group, and other symbols are
as defined above, in the presence of a reducing agent as desired,
under light irradiation. Item 2. The production method according to
Item 1, wherein R.sup.1 represents R.sup.11--Y-- or
(R.sup.11--).sub.2N--, Y represents a bond, oxygen, or sulfur, and
R.sup.11 independently represents, in each occurrence, a
hydrocarbon group that optionally has one or more substituents.
Item 3. The production method according to Item 2, wherein R.sup.1
represents R.sup.11--Y--, Y represents a bond, and R.sup.11
represents an aryl group that optionally has one or more
substituents, or an alkyl group that optionally has one or more
substituents.
Item 4.
[0013] The production method according to Item 2, wherein R.sup.1
represents R.sup.11--Y--, Y represents --O--C(.dbd.O)-- or
--O--C(.dbd.S)--, and R.sup.11 represents an aliphatic hydrocarbon
group that optionally has one or more substituents.
Item 5.
[0014] The production method according to Item 2, wherein R.sup.1
represents (R.sup.11--).sub.2N--C(.dbd.O)-- and R.sup.11
independently represents, in each occurrence, an aliphatic
hydrocarbon group that optionally has one or more substituents.
P Item 6
[0015] The production method according to any one of Item 1 to 5,
wherein RA represents fluorine.
Item 7.
[0016] The production method according to any one of Items 1 to 6,
wherein R.sup.4a represents hydrogen, R.sup.4b represents hydrogen,
R.sup.2 represents hydrogen, a hydrocarbon group that optionally
has one or more substituents, or an alkoxycarbonyl group that
optionally has one or more substituents, R.sup.5a represents
hydrogen, and R.sup.5b represents hydrogen.
Item 8.
[0017] The production method according to any one of Items 1 to
7,
wherein
[0018] X.sup.1 represents
halogen, an alkylsulfonyloxy group, or an arylsulfonyloxy
group.
Item 9.
[0019] The production method according to any one of Items 1 to 8,
wherein
X.sup.2 represents
--SO.sub.2R,
--SR,
--S (.dbd.O) R,
--SeR,
--TeR,
--Cl
--Br,
--PR.sub.2, or
--P(.dbd.O)R.sub.2,
[0020] wherein R independently represents, in each occurrence, an
organic group.
Item 10.
[0021] The production method according to Item 9, wherein X.sup.2
represents --SO.sub.2R, wherein R is an organic group.
Item 11.
[0022] The production method according to any one of Items 1 to 10,
wherein the reducing agent is a nitrogen-containing unsaturated
heterocyclic compound having an N--H moiety.
Item 12.
[0023] The production method according to any one of Items 1 to 11,
wherein the reducing agent is a compound represented by formula
(4):
##STR00010##
wherein R.sup.ha, R.sup.hb, R.sup.hc, and R.sup.hd are the same or
different, and each represents alkyl.
Item 13.
[0024] The production method according to any one of Items 1 to 12,
wherein the reaction of step A is performed in the presence of a
catalyst.
Item 14.
[0025] The production method according to Item 13, wherein the
catalyst is at least one member selected from the group consisting
of transition metal complexes and organic dye compounds.
Item 15.
[0026] A method for producing a compound represented by formula
(1a):
##STR00011##
wherein R.sup.1 independently represents, in each occurrence, an
organic group, R.sup.A independently represents, in each
occurrence, hydrogen or fluorine, R.sup.4a independently
represents, in each occurrence, hydrogen or an organic group,
R.sup.4b independently represents, in each occurrence, hydrogen or
an organic group, and R.sup.2 represents hydrogen or an organic
group; the method comprising step Aa of reacting a compound
represented by formula (2):
##STR00012##
wherein X.sup.1 represents a leaving group, and other symbols are
as defined above, with a compound represented by formula (3):
##STR00013##
wherein X.sup.2 represents a leaving group, and other symbols are
as defined above, in the presence of a reducing agent as desired,
under light irradiation.
Item 16.
[0027] A compound represented by formula (1):
##STR00014##
wherein R represents an organic group, R.sup.A represents hydrogen
or fluorine, R.sup.4a represents hydrogen or an organic group,
R.sup.4b represents hydrogen or an organic group, R.sup.2
represents an organic group, R.sup.5a represents hydrogen or an
organic group, and R.sup.5b represents hydrogen or an organic
group, with the proviso that when R.sup.1 represents a
perfluoroalkyl group, R.sup.2 represents an alkyl group having two
or more carbon atoms, or an ester group having three or more carbon
atoms.
Item 17.
[0028] The compound according to Item 16,
wherein R.sup.1 represents R.sup.11--Y--, Y represents a bond,
R.sup.11 represents an aryl group that optionally has one or more
substituents, or an alkyl group that optionally has one or more
substituents, represents hydrogen or fluorine, and R.sup.2
represents hydrogen or an organic group.
Item 18.
[0029] The compound according to Item 17, wherein R.sup.A
represents fluorine.
Item 19.
[0030] The compound according to Item 17 or 18,
wherein R.sup.4a represents hydrogen, R.sup.4b represents hydrogen,
R.sup.2 represents hydrogen, an alkoxycarbonyl group that
optionally has one or more substituents, an aryl group that
optionally has one or more substituents, or an alkyl group that
optionally has one or more substituents, R.sup.5a represents
hydrogen, and R.sup.5b represents hydrogen.
[0031] Item 20.
[0032] The compound according to Item 16, wherein
R.sup.1 represents R.sup.11--Y--, Y represents --O--C(.dbd.O)-- or
--O--C(.dbd.S)--, R.sup.11 represents an aliphatic hydrocarbon
group that optionally has one or more substituents, R.sup.A
represents hydrogen or fluorine, and R.sup.2 represents hydrogen or
an organic group.
Item 21.
[0033] The compound according to Item 20, wherein R.sup.A
represents fluorine.
Item 22.
[0034] The compound according to Item 20 or 21,
wherein R.sup.4a represents hydrogen, R.sup.4b represents hydrogen,
R.sup.2 represents hydrogen, an alkoxycarbonyl group that
optionally has one or more substituents, an aryl group that
optionally has one or more substituents, or an alkyl group that
optionally has one or more substituents, R.sup.5a represents
hydrogen, and R.sup.5b represents hydrogen.
Item 23.
[0035] The compound according to Item 16,
wherein R.sup.1 represents R.sup.11--Y--, Y represents
--O--C(--O--)-- or --O--C(.dbd.S)--, R.sup.11 represents an
aliphatic hydrocarbon group that optionally has one or more
substituents, R.sup.A represents hydrogen or fluorine, and R.sup.2
represents hydrogen or an organic group.
[0036] Item 24.
[0037] The compound according to Item 16,
wherein R.sup.1 represents (R.sup.11--).sub.2N--C(--O--)--,
R.sup.11 independently represents, in each occurrence, an aliphatic
hydrocarbon group that optionally has one or more substituents,
R.sup.A represents hydrogen or fluorine, R.sup.4a represents
hydrogen, R.sup.4b represents hydrogen, R.sup.2 represents hydrogen
or an organic group, R.sup.5a represents hydrogen, and R.sup.5b
represents hydrogen or an organic group.
Item 25.
[0038] The compound according to Item 24, wherein R represents
fluorine.
Advantageous Effects of Invention
[0039] The present disclosure provides an efficient, novel method
for producing a compound having a fluoromethylene group.
DESCRIPTION OF EMBODIMENTS
Terms
[0040] The symbols and the abbreviations in this specification are
to be interpreted as having the general meanings in the related
technical field to which the present disclosure pertains, according
to the context of this specification, unless otherwise
specified.
[0041] In this specification, the terms "comprise" and "contain"
encompass the meanings of consisting essentially of and consisting
of.
[0042] The steps, treatments, or operations in this specification
can be performed at room temperature unless otherwise
specified.
[0043] In this specification, room temperature refers to a
temperature in a range of 10 to 40.degree. C.
[0044] In this specification, "C.sub.n-m" (herein, n and m are each
natural numbers) indicates that the carbon number is n or more and
m or less, as conventionally used in the field of organic
chemistry.
[0045] In this specification, the term "fluoromethylene" includes
monofluoromethylene and difluoro methylene unless otherwise
specified.
[0046] In this specification, unless otherwise specified, examples
of "halogen atom" include fluorine, chlorine, bromine, and
iodine.
[0047] In this specification, unless otherwise specified, the term
"organic group" refers to a group containing at least one carbon
atom as its constituent atom.
[0048] In this specification, unless otherwise specified, examples
of "organic group" include hydrocarbon, cyano, carboxy, alkoxy,
ester, ether, and acyl.
[0049] In this specification, unless otherwise specified, the term
"hydrocarbon" refers to a group containing at least one carbon atom
and at least one hydrogen atom as its constituent atoms.
[0050] In this specification, unless otherwise specified, examples
of "hydrocarbon" include aliphatic hydrocarbon, aromatic
hydrocarbon (aryl), and combinations thereof.
[0051] In this specification, unless otherwise specified, the term
"aliphatic hydrocarbon" may be linear, branched, or cyclic
aliphatic hydrocarbon, or a combination thereof.
[0052] In this specification, unless otherwise specified, the term
"aliphatic hydrocarbon" may be saturated or unsaturated aliphatic
hydrocarbon.
[0053] In this specification, unless otherwise specified, examples
of "aliphatic hydrocarbon" include alkyl, alkenyl, alkynyl, and
cycloalkyl.
[0054] In this specification, unless otherwise specified, the term
"alkyl" refers to, for example, linear or branched, primary,
secondary, or tertiary C.sub.1-15 alkyl (e.g., C.sub.1-12 alkyl and
C.sub.1-10 alkyl), such as methyl, ethyl, propyl (e.g., n-propyl
and isopropyl), butyl (n-butyl, isobutyl, sec-butyl, tert-butyl),
pentyl (e.g., n-pentyl, tert-pentyl, neopentyl, isopentyl,
sec-pentyl, and 3-pentyl), hexyl, heptyl, octyl, nonyl, and
decyl.
[0055] In this specification, the term "fluoroalkyl" refers to
alkyl having at least one hydrogen atom replaced by a fluorine
atom.
[0056] In this specification, the number of fluorine atoms in the
"fluoroalkyl" may be one or more (e.g., 1 to 3, 1 to 6, 1 to 12, or
1 to the maximum replaceable number).
[0057] The term "fluoroalkyl" includes perfluoroalkyl. The term
"perfluoroalkyl" refers to alkyl having all hydrogen atoms replaced
by fluorine atoms.
[0058] In this specification, unless otherwise specified, the term
"alkenyl" refers to, for example, linear or branched C.sub.1-10
alkenyl, such as vinyl, 1-propenyl, isopropenyl,
2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl,
2-ethyl-l-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,
4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl,
and 5-hexenyl.
[0059] In this specification, unless otherwise specified, the term
"alkynyl" refers to, for example, linear or branched C.sub.2-6
alkynyl, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl,
2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl,
4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, and
5-hexynyl.
[0060] In this specification, unless otherwise specified, the term
"cycloalkyl" refers to, for example, C.sub.3-10 cycloalkyl
(preferably C.sub.4-10 cycloalkyl), such as cyclopentyl,
cyclohexyl, and cycloheptyl.
[0061] In this specification, unless otherwise specified, the term
"alkoxy" refers to, for example, a group represented by RO--
(wherein R represents alkyl).
[0062] In this specification, unless otherwise specified, the term
"ester" refers to, for example, a group represented by formula
RCO.sub.2-- (wherein R represents alkyl).
[0063] In this specification, unless otherwise specified, the term
"ether" refers to a group having an ether bond (--O--) and examples
of ether include polyether. Examples of polyether include groups
represented by formula R.sup.a--(O--R.sup.b).sub.n-- (wherein
R.sup.a represents alkyl, R.sup.b, in each occurrence, is the same
or different, and represents alkylene, and n is an integer of 1 or
more). Alkylene is a divalent group formed by removing one hydrogen
atom from the alkyl group.
[0064] In this specification, unless otherwise specified, the term
"acyl" includes alkanoyl. In this specification, unless otherwise
specified, the term "alkanoyl" refers to, for example, a group
represented by RCO-- (wherein R represents alkyl).
[0065] In this specification, unless otherwise specified, the term
"aromatic group" includes aryl and heteroaryl.
[0066] In this specification, examples of "aryl" include C.sub.6-14
aryl (e.g., C.sub.6-10 aryl), such as phenyl and naphthyl.
[0067] In this specification, examples of "heteroaryl" include 5-
to 14-membered (monocyclic, dicyclic, or tricyclic) heterocyclic
groups containing, in addition to carbon, 1 to 4 heteroatoms
selected from the group consisting of nitrogen, sulfur, and oxygen
as an annular atom.
[0068] In this specification, examples of "heteroaryl" include (1)
monocyclic aromatic heterocyclic groups, such as furyl, thienyl,
pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl,
pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl,
oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, and triazinyl;
and
(2) polycyclic (e.g., dicyclic) aromatic heterocyclic groups, such
as quinolyl, isoquinolyl, quinazolvl, quinoxalyl, benzofuryl,
benzothienyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl,
benzimidazolyl, benzotriazolyl, indolyl, indazolyl, pyrrolo
pyrazinyl, imidazo pvridinyl, imidazo pyrazinyl, imidazo thiazolyl
pyrazolo pyridinyl, pyrazolo thienyl, and pvrazolo thoriadinyl.
[0069] In the specification, examples of "aromatic rings" include
(1) aromatic carbon rings such as a benzene ring and a naphthalene
ring, and (2) 5- or 6-membered monocyclic aromatic heterocyclic
rings having as the ring-constituting atoms, in addition to carbon
atoms, 1 to 3 heteroatoms selected from oxygen, sulfur, and
nitrogen. Specific examples of such 5- or 6-membered monocyclic
aromatic heterocyclic rings include a furan ring, a thiophene ring,
a pyrrole ring, an oxazole ring, an isoxazol ring, a thiazole ring,
an isothiazole ring, an imidazole ring, a pyrazole ring, a
1,2,3-oxadiazole ring, a 1,2,4-oxadiazole ring, a 1,3,4-oxadiazole
ring, a furazan ring, a 1,2,3-thiadiazole ring, a 1,2,4-thiadiazole
ring, a 1,3,4-thiadiazole ring, a 1,2,3-triazole ring, a
1,2,4-triazole ring, a tetrazole ring, a pyridine ring, a
pyridazine ring, a pyrimidine ring, a pyrazine ring, a triazine
ring, and the like.
[0070] In this specification, examples of a "non-aromatic
hydrocarbon ring" include C.sub.3-8 non-aromatic hydrocarbon rings.
Specific examples include:
(1) C.sub.3-8 cycloalkanes, such as cyclopropane, cyclobutane,
cyclopentane, cyclohexane, cycloheptene, and cyclooctane; (2)
C.sub.5-8 cycloalkenes, such as cyclopentene, cyclohexene,
cycloheptene, and cyclooctene; (3) C.sub.5-8 cycloalkadienes, such
as cyclopentadiene, cyclohexadiene, cycloheptadiene, and
cyclooctadiene; and (4) C.sub.5-8 bridged-ring hydrocarbons, such
as bicyclo[2.1.0]pentane, bicyclo[2.2.1]heptane,
bicyclo[3.2.1]octane, bicyclo[2.2.1]hept-2-ene, and
tricyclo[2.2.1.0]heptane.
[0071] In this specification, examples of "non-aromatic
heterocyclic rings" include 3- to 8-membered non-aromatic
heterocyclic rings and the like. Specific examples include oxirane,
azetidine, oxetane, thietane, pyrrolidine, dihydrofuran,
tetrahydrofuran, tetrahydrothiophene, imidazolidine, cxazolidine,
isoxazoline, piperidine, dihydropyran, tetrahydropyran,
tetrahydrothiopyran, morpholine, thiomorpholine, piperazine,
dihydrooxazine, tetrahydrooxazine, dihydropyrimidine,
tetrahydropyrimidine, azepane, oxepane, thiepane, oxazepane,
thiazepane, azocane, oxocane, thiocane, oxazocane, and
thiazocane.
Production Method: Compound (1)
[0072] The method for producing a compound represented by formula
(1) (in the specification, sometimes referred to as "compound
(1)"):
##STR00015##
wherein R.sup.1 represents an organic group, R.sup.A represents
hydrogen or fluorine, R.sup.4a represents hydrogen or an organic
group, R.sup.4b represents hydrogen or an organic group, R.sup.5a
represents hydrogen or an organic group, R.sup.5b represents
hydrogen or an organic group, and R.sup.2 represents hydrogen or an
organic group; or R.sup.2 may be connected to R.sup.4a to form a
ring; the method comprising step A of reacting a compound
represented by formula (2):
##STR00016##
wherein X.sup.1 represents a leaving group, and other symbols are
as defined above, with a compound represented by formula (3):
##STR00017##
wherein X.sup.2 represents a leaving group, and other symbols are
as defined above, in the presence of a reducing agent as desired
under light irradiation.
[0073] In one preferable embodiment of the present invention,
R.sup.1 represents R.sup.11--Y-- or (R.sup.11--).sub.2N--, Y
represents a bond, oxygen, or sulfur, and R.sup.11 independently
represents, in each occurrence, a hydrocarbon group that may have
one or more substituents.
[0074] In a more preferable embodiment of the present
invention,
R.sup.1 represents R.sup.11--Y--, Y represents a bond, and R.sup.11
represents an aryl group that may have one or more substituents, or
an alkyl group that may have one or more substituents.
[0075] R.sup.11 preferably represents an aryl group or a
perfluoroalkyl group.
[0076] In another preferable embodiment of the present
invention,
R.sup.1 represents R.sup.11--Y--, Y represents --O--C(--O--)-- or
--O--C(.dbd.S)--, and R.sup.11 represents an aliphatic hydrocarbon
group that may have one or more substituents. R.sup.11 preferably
represents a C.sub.1-6 alkyl group or a C.sub.7-11 aralkyl group
(e.g., benzyl).
[0077] In yet another more preferable embodiment of the present
invention,
R.sup.1 represents (R.sup.11--).sub.2N--C(.dbd.O)-- and R.sup.11
independently represents, in each occurrence, a hydrocarbon group
that may have one or more substituents.
[0078] Preferably, R.sup.11 independently represents, in each
occurrence, C.sub.1-6 alkyl.
[0079] R.sup.A preferably represents fluorine.
[0080] xamples of the "ring" formed by connecting R.sup.2 to
R.sup.4 include aromatic rings, non-aromatic hydrocarbon rings, and
non-aromatic heterocyclic rings.
[0081] Examples of substituents of the ring include halogen, nitro,
cyano, amino, hydroxy, carboxy, alkyl, alkenyl, and alkynyl.
[0082] R.sup.2 preferably represents
hydrogen, a hydrocarbon group that may have one or more
substituents, or an alkoxycarbonyl group that may have one or more
substituents.
[0083] R.sup.2 more preferably represents
hydrogen, C.sub.1-5 , alkyl that may have one or more substituents,
C.sub.6-1. aryl that may have one or more substituents, or
C.sub.1-6 alkoxy-carbonyl that may have one or more
substituents.
[0084] R.sup.4a preferably represents hydrogen.
[0085] R.sup.4b preferably represents hydrogen.
[0086] R.sup.5a preferably represents hydrogen.
[0087] R.sup.5b preferably represents hydrogen.
[0088] R.sup.2 preferably represents
hydrogen, a hydrocarbon group that may have one or more
substituents, or an alkoxycarbonyl group that may have one or more
substituents; R.sup.4a preferably represents hydrogen, R.sup.4b
preferably represents hydrogen, R.sup.5a preferably represents
hydrogen, and R.sup.5 preferably represents hydrogen.
[0089] Examples of the leaving group represented by X.sup.1 include
halogen (e.g., fluorine, chlorine, bromine, and iodine),
alkylsulfonyloxy (e.g., C.sub.1-6 alkylsulfonyloxy, such as
methanesulfonyloxy and trifluoromethanesulfonyloxy); and
arylsulfonyloxy (e.g., C.sub.6-10 arylsulfonyloxy, such as benzene
sulfonyloxy and p-toluenesulfonyloxy).
[0090] X.sup.1 preferably represents halogen, an alkylsulfonyloxy
group, or an arylsulfonyloxy group.
[0091] X.sup.2 preferably represents
--SO.sub.2R,
--SR,
--S(.dbd.O)R,
--SeR,
--TeR,
--Cl,
--Br,
--I,
--PR.sub.2, or
--P(.dbd.O)R.sub.2,
[0092] wherein R independently represents, in each occurrence, an
organic group.
[0093] X.sup.2 more preferably represents --SO.sub.2R, wherein R is
an organic group.
[0094] The amount of compound (3) used in step A is preferably in
the range of 1.0 to 20.0 moles, more preferably in the range of 1.3
to 10 moles, and even more preferably in the range of 1.5 to 5
moles, per mole of compound (2).
[0095] The reaction of step A is preferably performed as desired in
the presence of a reducing agent.
[0096] The reducing agent may be an inorganic or organic reducing
agent. Examples of the reducing agent include hydrogen, formic
acid, ammonium formate, sodium formate, formic acid triethylamine,
triethylsilan, tetramethyl disiloxane, polymethylhydrosiloxane,
NaBH.sub.3CN, NHCBH.sub.3 (N-heterocyclic carbene boranes), and a
nitrogen-containing unsaturated heterocyclic compound having an
N--H moiety (imino group).
[0097] Preferable examples of the reducing agent include a
nitrogen-containing unsaturated heterocyclic compound having an
N--H moiety.
[0098] Preferable examples of the "nitrogen-containing unsaturated
heterocyclic compound having an N--H moiety" that can be used as a
reducing agent include a compound represented by formula (4)
(sometimes referred to in this specification as "compound
(4)"),
##STR00018##
wherein R.sup.3a, R.sup.3b, R.sup.3c, and R.sup.3d are the same or
different, and each represents alkyl.
[0099] R.sup.3a preferably represents C.sub.1-6 alkyl, and more
preferably methyl or ethyl.
[0100] R.sup.3b preferably represents C.sub.1-6 alkyl, and more
preferably methyl or ethyl.
[0101] R.sup.3c preferably represents C.sub.1-6 alkyl, and more
preferably methyl or ethyl.
[0102] R.sup.3d preferably represents C.sub.1-6 alkyl, and more
preferably methyl or ethyl.
[0103] More preferable examples of the reducing agent that can be
used in the present disclosure include compounds represented by the
formulae below. These compounds are "Hantzsch esters" (sometimes
abbreviated in this specification as "HEH").
##STR00019##
[0104] Such reducing agents can be used alone or in a combination
of two or more.
[0105] In the reaction of step A, an acid-removing agent, such as
amine, can be optionally used.
[0106] When compound (4) is used, it is preferable not to use other
amines.
[0107] When the reducing agent is used in step A, the amount of the
reducing agent is preferably within 0.5 to 10 moles, more
preferably 1.0 to 5.0 moles, and even more preferably 1.2 to 3.0
moles, per mole of the compound represented by formula (2), which
is a substrate.
[0108] The reaction of step A can be performed in the presence of a
catalyst or in the substantial or complete absence of a
catalyst.
[0109] The reaction of step A is preferably performed in the
presence of a catalyst.
[0110] Examples of the catalyst used in the present disclosure
include transition metal complexes and organic dye compounds.
[0111] Examples of the kinds of central metal contained in the
transition metal complexes that can be used in the present
disclosure include cobalt, ruthenium, rhodium, rhenium, iridium,
nickel, palladium, osmium, and platinum.
[0112] Preferable examples of the kinds of central metal include
ruthenium, iridium, and palladium.
[0113] Examples of ligands of the transition metal complexes that
can be used in the present disclosure include nitrogen-containing
compounds, oxygen-containing compounds, and sulfur-containing
compounds.
[0114] Examples of "nitrogen-containing compounds" used as ligands
include diamine compounds (e.g., ethylenediamine) and
nitrogen-containing heterocyclic compounds (e.g., pyridine,
bipyridine, phenanthroline, pyrrole, indole, carbazole, imidazole,
pyrazole, quinoline, isoquinoline, acridine, pyridazine,
pyrimidine, pyrazine, phthalazine, quinazoline, and
quinoxaline.)
[0115] Examples of "oxygen-containing compounds" used as ligands
include diketones (e.g., dipivaloyl methane) and oxygen-containing
heterocyclic compounds (e.g., furan, benzofuran, oxazol, pyran,
pyrone, coumarin, and benzopyrone).
[0116] Examples of "sulfur-containing compounds" used as ligands
include sulfur-containing heterocyclic compounds (e.g., thiophene,
thionaphthene, and thiazole).
[0117] In the transition metal complex, the number of ligands of
these compounds can be one or more. However, needless to say, the
number of ligands may not necessarily be clear.
[0118] When a catalyst is used in the reaction of step A, the
amount of the catalyst in step A is preferably within 0.0001 to 0.1
moles, more preferably 0.001 to 0.05 moles, and even more
preferably 0.005 to 0.02 moles, per mole of compound (2).
[0119] The organic dye compound that can be used in the present
disclosure can be a compound containing no metal atom in the
molecule.
[0120] Examples of such organic dye compounds include rose bengal,
erythrosine, eosine (e.g., eosine B and cosine Y), acriflavine,
riboflavine, and thionine.
[0121] Preferable examples of catalysts include [Ir{dF(CF.sub.3)
ppy}.sub.2(dtbpY) ]PF.sub.6, [Ir(dtbbPY)(PIDY).sub.2][PF.sub.6],
Ir(PPY).sub.3, Ru(bpY).sub.3Cl.sub.2.6H.sub.2O ,
[Ru(bpz).sub.3][PF.sub.6].sub.2, [Ru(bpm).sub.3][Cl] .sub.2,
[Ru(bpy).sub.2(phen-5-NH.sub.2)][PE.sub.6].sub.2,
[Ru(bpy).sub.3][PF.sub.6].sub.2, Ru(phen).sub.3Cl.sub.2,
Cu(dap).sub.2 chloride, 9-mesityl-10-methyl acridiniumperchlorate,
Ir(ppy).sub.3, and Pd(PPh.sub.3).sub.4.
[0122] The catalysts can be used alone or in a combination of two
or more.
[0123] A photoredox catalyst can be preferably used as the catalyst
used in step A.
[0124] The catalyst used in step A may be carried by a carrier
(e.g., zeolite).
[0125] The reaction of step A can be performed in the presence of a
solvent or in the substantial or complete absence of a solvent.
[0126] The reaction of step A is preferably performed in the
presence of a solvent.
[0127] Examples of solvents used in the present disclosure include
dimethylformamide (DMF), toluene, CH.sub.3CN, ether,
tetrahydrofuran (THF), benzene, dimethylsulfoxide (DMSO), hexane,
and benzotrifluoride (BTF).
[0128] These solvents can be used alone or in a combination of two
or more.
[0129] When the reaction of step A starts, the concentration of
compound (2) in the mixture of the reaction system is preferably
within 1 to 10000 mM, more preferably within 10 to 1000 mM, and
even more preferably within 50 to 200 mM.
[0130] When the reaction of step A starts, the concentration of
compound (3) in the mixture of the reaction system is preferably
within 50 to 50000 mM, more preferably within 100 to 5000 mM, and
even more preferably within 300 to 1000 mM.
[0131] When the catalyst is used in the reaction of step A, the
concentration of the catalyst in the mixture of the reaction system
is preferably within 0.01 to 100 mM, more preferably within 0.1 to
50 mM, and even more preferably within 0.5 to 20 mM.
[0132] Step A can be performed by mixing compound (2) and compound
(3) with, as desired, a reducing agent, a catalyst, and a
solvent.
[0133] Conventional methods can be used for the mixing.
[0134] In the mixing, all of the substances can be simultaneously
mixed, or sequentially or gradually mixed.
[0135] The reaction of step A is performed under light
irradiation.
[0136] Any irradiation light can be used for light irradiation as
long as light can start and/or promote the reaction of step A.
Examples of the light source include a low-pressure,
medium-pressure, or high-pressure mercury-vapor lamp, tungsten
lamp, and light-emitting diode (LED).
[0137] The irradiation light can be preferably visible light.
[0138] The irradiation light is preferably light having a
wavelength of 300 to 600 nm, and more preferably light having a
wavelength of 400 to 500 nm.
[0139] The irradiation time is preferably within 1 to 24 hours, and
more preferably within 10 to 18 hours.
[0140] The light irradiation can start before, during, at the same
time as, or after mixing.
[0141] The intensity of light irradiation may be such that energy
for starting and/or promoting the reaction of step A is supplied.
For example, the intensity of light irradiation can be suitably
adjusted by adjusting, based on common technical knowledge, the
output of the light source, the distance between the light source
and the reaction system of step A, etc. so that the reaction of
step A suitably proceeds.
[0142] The reaction of step A can be performed in the presence of
an inert gas. Examples of the inert gas include nitrogen and
argon.
[0143] The reaction temperature in step A is preferably within 0 to
120.degree. C., more preferably within 10 to 80.degree. C., and
even more preferably within 20 to 60.degree. C.
[0144] When the reaction temperature is within the above ranges,
the reaction of step A sufficiently proceeds.
[0145] The reaction temperature being within the above ranges is
advantageous in view of costs, and undesirable side reaction is
inhibited.
[0146] The reaction time in step A is preferably within 1 to 24
hours, more preferably within 5 to 18 hours, and even more
preferably within 10 to 15 hours.
[0147] When the reaction time is within the above ranges, the
reaction of step A sufficiently proceeds.
[0148] The reaction time being within the above ranges is
advantageous in view of costs, and undesirable side reaction is
inhibited.
[0149] The reaction of step A can be preferably performed in
batches or in a flow system.
[0150] Compound (1) obtained by the production method of the
present disclosure can be purified as desired by a known
purification method, such as solvent extraction, drying,
filtration, distillation, concentration, and a combination
thereof.
[0151] According to the production method of the present
disclosure, the inversion rate of compound (2), which is a starting
material, is preferably 40% or more, more preferably 60% or more,
and even more preferably 80% or more.
[0152] According to the production method of the present
disclosure, the selectivity of compound (1) is preferably 70% or
more, and more preferably 80% or more.
[0153] According to the production method of the present
disclosure, the yield of compound (1) is preferably 40% or more,
and more preferably 60% or more.
[0154] Compound (1) obtained by the production method of the
present disclosure can be used, for example, as a pharmaceutical
intermediate.
Production Method: Compound (1a)
[0155] The present specification discloses a method for producing a
compound represented by formula (1a):
##STR00020##
wherein R.sup.1 independently represents, in each occurrence, an
organic group, R.sup.A independently represents, in each
occurrence, hydrogen or fluorine, R.sup.4 independently represents,
in each occurrence, hydrogen or an organic group, and R.sup.4b
independently represents, in each occurrence, hydrogen or an
organic group, and R.sup.2 represents hydrogen or an organic group;
the method comprising step Aa of reacting a compound represented by
formula (2):
##STR00021##
wherein X.sup.1 represents a leaving group, and other symbols are
as defined above, with a compound represented by formula (3):
##STR00022##
wherein X.sup.2 represents a leaving group, and other symbols are
as defined above, in the presence of a reducing agent as desired,
under light irradiation.
[0156] Step Aa is the same as step A, except that the product to be
produced is different.
[0157] In other words, compound (1) and/or compound (1a) can be
produced using the substrate and the conditions of the reaction of
step A (or step Aa).
[0158] Accordingly, step Aa can be understood based on the
explanation of step A.
[0159] Here, in order to produce compound (Aa) more preferentially,
it is preferable to set the amount of compound (3) to be smaller
than the amount of compound (2).
[0160] Specifically, in this case, the molar ratio of compound (3)
to compound (2) can be preferably in the range of 0.9 to 0.1, and
more preferably in the range of 0.5 to 0.2.
[0161] In contrast, in order to produce compound (A) more
preferentially, it is preferable to set the amount of compound (3)
to be larger than the amount of compound (2).
[0162] Specifically, in this case, the molar ratio of compound (3)
to compound (2) can be preferably in the range of 1.1 to 10, and
more preferably in the range of 2 to 5.
Compound (1)
[0163] This specification also discloses the following compound
(which is sometimes referred to as "compound (1)").
[0164] A compound represented by formula (1):
##STR00023##
wherein R.sup.1 represents an organic group, represents hydrogen or
fluorine, R.sup.4a represents hydrogen or an organic group,
R.sup.4b represents hydrogen or an organic group, R.sup.2
represents hydrogen or an organic group, R.sup.5a represents
hydrogen or an organic group, and R.sup.3b represents hydrogen or
an organic group, with the proviso that when R.sup.1 represents a
perfluoroalkyl group, R.sup.2 represents an alkyl group having two
or more carbon atoms, or an ester group having three or more carbon
atoms).
Embodiment 1a1
[0165] In compound (1), it is preferable that
R.sup.1 represents R.sup.11--Y-- and Y represents a bond, R.sup.11
represents an aryl group that may have one or more substituents, or
an alkyl group that may have one or more substituents, R.sup.A
represents hydrogen or fluorine, and R.sup.2 represents hydrogen or
an organic group.
[0166] R.sup.11 preferably represents an aryl group or a
perfluoroalkyl group.
[0167] R.sup.11 more preferably represents a C.sub.6-10 aryl group
or a C.sub.1-10 perfluoroalkyl group.
[0168] R.sup.A preferably represents fluorine.
[0169] R.sup.2 preferably represents
hydrogen, a hydrocarbon group that may have one or more
substituents, or an alkoxycarbonyl group that may have one or more
substituents.
[0170] R.sup.2 more preferably represents
hydrogen, an alkoxycarbonyl group that may have one or more
substituents, an aryl group that may have one or more substituents,
or an alkyl group that may have one or more substituents
[0171] R.sup.2 more preferably represents
hydrogen, a C.sub.1-6 alkyl group that may have one or more
substituents, a C.sub.6-14 aryl group that may have one or more
substituents, or a C.sub.1-6 alkoxy-carbonyl group that may have
one or more substituents.
[0172] R.sup.2 is even more preferably hydrogen, a C.sub.1-6 alkyl
group, a C.sub.6-14 aryl group, or a C.sub.1-6, alkoxy-carbonyl
group.
[0173] R.sup.4a preferably represents hydrogen.
[0174] R.sup.4b preferably represents hydrogen.
[0175] R.sup.5a preferably represents hydrogen.
[0176] R.sup.5b preferably represents hydrogen.
[0177] It is preferable that
R.sup.4a represents hydrogen or an organic group; R.sup.4b
represents hydrogen or an organic group; R.sup.2 represents
hydrogen, an alkoxycarbonyl group that may have one or more
substituents, an aryl group that may have one or more substituents,
or an alkyl group that may have one or more substituents; R.sup.5a
represents hydrogen; and R.sup.5b represents hydrogen.
Embodiment 1a2
[0178] In compound (1), it is preferable that
R represents R.sup.11--Y--; Y represents --O--C(.dbd.O)-- or
--O--C(.dbd.S)--; R.sup.11 represents an aliphatic hydrocarbon
group that may have one or more substituents; R.sup.A represents
hydrogen or fluorine; and R.sup.2 represents hydrogen or an organic
group.
[0179] It is preferable that R.sup.A represents fluorine.
[0180] It is preferable that R.sup.2 represents hydrogen, an
alkoxycarbonyl group that may have one or more substituents, an
aryl group that may have one or more substituents, or an alkyl
group that may have one or more substituents.
[0181] It is preferable that R.sup.2 represents hydrogen,
a C.sub.1-6 alkoxy-carbonyl group that may have one or more
substituents, a C.sub.6-14 aryl group that may have one or more
substituents, or a C.sub.1-6 alkyl group that may have one or more
substituents.
[0182] R.sup.4a preferably represents hydrogen.
[0183] R.sup.4b preferably represents hydrogen.
[0184] R.sup.5a preferably represents hydrogen.
[0185] R.sup.5b preferably represents hydrogen.
[0186] It is preferable that
R.sup.4a represents hydrogen, R.sup.4b represents hydrogen, R.sup.2
represents hydrogen, an alkoxycarbonyl group that may have one or
more substituents, an aryl group that may have one or more
substituents, or an alkyl group that may have one or more
substituents, R.sup.5a represents hydrogen, and R.sup.5b represents
hydrogen.
Embodiment 1a3
[0187] In compound (I), it is preferable that
R.sup.1 represents R.sup.11--Y--, Y represents --O--C(.dbd.O)-- or
--O--C(.dbd.S)--, R.sup.11 represents an aliphatic hydrocarbon
group that may have one or more substituents, R.sup.A represents
hydrogen or fluorine, and R.sup.2 represents hydrogen or an organic
group.
Embodiment 1a4
[0188] In compound (1), it is preferable that
R.sup.1 represents (R.sup.11).sub.2N.sup.-C(.dbd.O)--, R.sup.11
independently represents, in each occurrence, an aliphatic
hydrocarbon group that may have one or more substituents, R.sup.A
represents hydrogen or fluorine, and R.sup.2 represents hydrogen or
an organic group.
[0189] It is preferable that R.sup.11 independently represents, in
each occurrence, C.sub.1-6 alkyl.
[0190] R.sup.A preferably represents fluorine.
Production Method: Production Method of Compound (1B)
[0191] The present specification further discloses a method for
producing a compound (which is sometimes referred to in this
specification as "compound (1B)") represented by formula (1B):
##STR00024##
wherein R.sup.1 represents an organic group, R.sup.A represents
hydrogen or fluorine, R.sup.B1 represents hydrogen or an organic
group, R.sup.B2 represents hydrogen or an organic group, and
R.sup.2 represents hydrogen or an organic group; the method
comprising step A.sup.2 of reacting a compound represented by
formula (2):
##STR00025##
wherein X.sup.1 represents a leaving group, and other symbols are
as defined above, with a compound represented by formula (3):
##STR00026##
[0192] wherein X.sup.2 represents a leaving group, and other
symbols are as defined above, and a compound represented by formula
(4):
##STR00027##
wherein the symbols are as defined above, in the presence of a
reducing agent under light irradiation.
[0193] The amount of compound (4) used in step A.sup.B is in the
range of 3 to 20 moles, more preferably in the range of 4 to 15
moles, and even more preferably in the range of 5 to 12 moles, per
mole of compound (2).
[0194] The other conditions and method of step A.sup.B can be the
same as the conditions and method of step A. The details are
described below.
[0195] The reaction of step A.sup.2 is performed under light
irradiation.
[0196] The irradiation light used in the light irradiation is not
particularly limited as long as it is light that starts and/or
promotes the reaction in step A. Examples of the light source
include low-, medium-, or high-pressure mercury lamps, tungsten
lamps, and light-emitting diodes (LEDs).
[0197] The irradiation light can be preferably visible light.
[0198] The irradiation light is preferably light having a
wavelength of 300 to 600 nm, and more preferably light having a
wavelength of 400 to 500 nm.
[0199] The irradiation time is preferably in the range of 1 to 24
hours, and more preferably in the range of 10 to 18 hours. The
light irradiation can start before, during, at the same time as, or
after mixing.
[0200] The intensity of light irradiation may be such that energy
for starting and/or promoting the reaction of step AB is supplied.
For example, the intensity of light irradiation can be suitably
adjusted by adjusting, based on common technical knowledge, the
output of the light source, the distance between the light source
and the reaction system of step A.sup.B, etc. so that the reaction
of step A.sup.B suitably proceeds.
[0201] The reaction of step A.sup.B can be performed in the
presence of an inert gas. Examples of the inert gas include
nitrogen and argon.
[0202] The reaction temperature in step A.sup.B is preferably
within 0 to 120.degree. C., more preferably within 10 to 80.degree.
C., and even more preferably within 20 to 60.degree. C.
[0203] When the reaction temperature is within the above ranges,
the reaction of the step A.sup.B sufficiently proceeds.
[0204] The reaction temperature being within the above ranges, is
advantageous in view of costs, and undesired side effects can be
reduced.
[0205] The reaction time in step A.sup.B is preferably within 1 to
24 hours, more preferably within 5 to 18 hours, and even more
preferably within 10 to 15 hours. When the reaction time is within
the above ranges, the reaction of step A.sup.B sufficiently
proceeds.
[0206] The reaction time being within the above ranges, it is
advantageous in view of costs, and undesired side effects can be
reduced.
[0207] The reaction of step A.sup.B can be preferably performed in
batches or in a flow system.
[0208] Compound (1B) obtained by the production method of the
present disclosure can be purified, as desired, by a known
purification method, such as solvent extraction, drying,
filtration, distillation, concentration, and a combination
thereof.
[0209] According to the production method of the present
disclosure, the inversion rate of compound (2), which is a starting
material, is preferably 40% or more, more preferably 60% or more,
and even more preferably 80% or more.
[0210] According to the production method of the present
disclosure, the selectivity of compound (1B) is preferably 70% or
more, and more preferably 80% or more.
[0211] According to the production method of the present
disclosure, the yield of compound (1B) is preferably 40% or more,
and more preferably 60% or more.
[0212] Compound (1B) obtained by the production method of the
present disclosure can be used, for example, as a phaLmaceutical
intermediate.
EXAMPLES
[0213] The present invention is detailed below with reference to
Examples; however, the present invention is not limited to
these.
[0214] The following abbreviations may be used in this
specification.
HEH: Hantzsch ester
TTMSS: Tris(trimethylsilyl)silane
[0215] DIEA: N,N-diisopropyl ethylamine bpy: 2,2'-bipyridine
[0216] In the Examples below, yields are isolated yields unless
otherwise specified.
Example 1
Production of Compounds 3a and 4a Under Various Conditions
[0217] Using the materials and conditions in Table 1, a solution
(solvent: 3 ml) containing compound 1a (0.5 mmol), compound 2a (1.5
or 3.0 equivalents), Hantzsch ester a (HEM), and amine (2
equivalents) was subjected to light irradiation in a glass tube in
the presence of a catalyst (1 mol %) using a white LED lamp (5 W)
for 12 hours.
[0218] As a result, compound 3a and/or compound 4a was obtained in
the NMR yields shown in Table 1.
##STR00028##
TABLE-US-00001 TABLE 1 1 Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O HEH
(1.2) Et.sub.3N 1.5 DMF 51 21 2 Ir(ppy) HEH (1.2) Et.sub.3N 1.5 DMF
20 20 3 Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O TTMSS (1.2) Et.sub.3N
1.5 DMF 13 0 4 Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O NaBH.sub.3CN
(1.2) Et.sub.3N 1.5 DMF 5 Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O HEH
(0.6) Et.sub.3N 1.5 DMF 21 6 Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O
HEH (0.6) DBU 1.5 DMF 0 9 7 Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O
HEH (0.6) DIEA 1.5 DMF 68 20 8
Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O HEH (0.6) DIEA 1.5
CH.sub.3Cl.sub.2 7 9 Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O HEH
(0.6) DIEA 1.5 MeCN 68 21 10 Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O
HEH (0.6) DIEA 2.0 MeCN 82 12 11
Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O HEH (0.6) DIEA 3.0 MeCN 91 9
12 Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O HEH (0.6) DIEA 3.0 MeCN 97
3 13 None HEH (0.6) DIEA 3.0 MeCN 0 0 14
Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O None DIEA 3.0 MeCN 53 3 15
Rucl.sub.2(bpy).sub.3.cndot.6H.sub.2O HEH (0.6) None 3.0 MeCN 14 0
indicates data missing or illegible when filed
Example 2
Production of Allyl Compound Using Difluoro Halo Alkyl Compound and
Allyl Sulfone Compound with Ru-Photoreduction Catalyst
[0219] Using the materials and conditions in Table 2, a DMF
solution containing compound 1, compound 2,
Ru(bpy).sub.3Cl.sub.2.6H.sub.2O (1 mol %), ester a (HEH), and
Et.sub.3N were subjected to light irradiation in a grass tube using
a white LED lamp (5 W) for 2 hours.
[0220] As a result, compound 3 was obtained in the yield shown in
Table 2. (Symbol c indicates the NMR yield in the table.)
TABLE-US-00002 TABLE 2 ##STR00029## entry 1 2 3 yield (%) 1
##STR00030## ##STR00031## ##STR00032## 3a 94 2 ##STR00033##
##STR00034## 3b 60 3.sup.b ##STR00035## ##STR00036## 3c 68 4
##STR00037## 2a ##STR00038## 3d 72 5 2b ##STR00039## 3e 72 6
##STR00040## ##STR00041## 3f 34 (69).sup.c 7 ##STR00042## 2a
##STR00043## 3g 57 8 2c ##STR00044## 3h 47 9 2d ##STR00045## 3i 60
10 ##STR00046## 2a ##STR00047## 3j 78 11 2d ##STR00048## 3k 74 12
##STR00049## 2a ##STR00050## 3l 45 13 1e 2d ##STR00051## 3m 63 14
##STR00052## 2a ##STR00053## 3n 72 15 1f 2b ##STR00054## 3o 60
Example 3
Examination of Effects of Light Irradiation
##STR00055##
[0222] In order to verify the effect of light irradiation using the
reaction under the conditions of the above scheme, light
irradiation in this system was turned on and off.
[0223] After 10 minutes of light irradiation, product 3a was formed
in the yield of 49%.
[0224] When the light source was turned off to stop light
irradiation, the reaction stopped quickly.
[0225] 26 hours later, when the light source was turned on to
restart light irradiation, the reaction was quickly restarted.
Example 4
##STR00056##
[0227] In addition to compounds 1 and 2 in the above Example, the
three-component radical reaction was tested in the Example by the
addition of alkene(1-octene 5a) under the conditions of Scheme T
above.
[0228] By the reaction of the three components, i.e.,
2-bromo-2,2-difluoroacetic acid ethyl 1b, 1-octene 5a, and
2-methoxycarbonyl-substituted allyl sulfone 2a, product 6a was
obtained in a yield of 50%.
[0229] By the reaction of the three components, i.e.,
perfluorcdecyl bromide 1e, 1-octene 5a, and 2-phenyl allyl sulfone
2a, compound 6b was obtained in a yield of 56%.
* * * * *